Zhou Yinwei, Wang Wenbo, Gu Han, Jiang Ying, Wang Xi, Su Xin, Shao Zhixiang, An Kang, Liang Rui, Ma Yuzhen, Wang Rui, Luo Lin
School of Pharmacy, Nantong University, Nantong, Jiangsu 226019, PR China.
School of Pharmacy, Nantong University, Nantong, Jiangsu 226019, PR China; Department of Pharmacy, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu 25300, PR China.
J Ethnopharmacol. 2025 Jul 24;351:120083. doi: 10.1016/j.jep.2025.120083. Epub 2025 Jun 2.
Buzhongyiqi Granules (BZYQ), a classical herbal formulation derived from Pi Wei Lun, is traditionally used to regulate Qi and blood circulation while enhancing immune function, particularly for gastrointestinal disorders. However, its protective effects and mechanisms on ulcerative colitis (UC) remain unclear.
This study aimed to identify the blood-entering bioactive components of BZYQ and elucidate its immune-modulatory mechanisms in UC using an integrated strategy combining medicinal chemistry, bioinformatics analysis, molecular docking, and experimental validation.
The chemical profile and serum pharmacochemistry components (SPCs) of BZYQ were identified via UPLC-QE-Orbitrap mass spectrometry. Network pharmacology and molecular docking predicted UC-related targets and pathways. In vivo, experimental colitis was induced via 3 % dextran sulfate sodium solution administration for 7 days, followed by 10-day BZYQ treatment. Anti-inflammatory effects were validated through flow cytometry, qPCR, Western blotting, and in vitro bone marrow-derived macrophage (BMDM) cultures.
Fifty-four compounds were identified in BZYQ, with seven SPCs (astragaloside IV, licoflavone A, 18β-glycyrrhizinic acid, glabrolide, ganoderic acid X, complanatuside, and isosakuranin) directly related to UC pathogenesis. Molecular docking confirmed high-affinity interactions between glabrolide and IL-6. BZYQ alleviated colitis by suppressing IL-6/STAT3 axis, reprogramming macrophage polarization, increasing regulatory T cell frequency, and suppressing naive CD4 T cell differentiation.
This study is the first to define BZYQ's component basis and cellular immunological mechanisms in UC alleviation. These findings contribute to the development and application of traditional Chinese medicine prescriptions.
补中益气颗粒（BZYQ）是源自《脾胃论》的经典中药配方，传统上用于调理气血循环并增强免疫功能，尤其适用于胃肠道疾病。然而，其对溃疡性结肠炎（UC）的保护作用及机制仍不清楚。
本研究旨在通过结合药物化学、生物信息学分析、分子对接和实验验证的综合策略，确定BZYQ的入血生物活性成分，并阐明其在UC中的免疫调节机制。
通过超高效液相色谱-四极杆-轨道阱质谱法鉴定BZYQ的化学图谱和血清药物化学成分（SPCs）。网络药理学和分子对接预测UC相关靶点和通路。在体内，通过给予3%葡聚糖硫酸钠溶液诱导实验性结肠炎7天，随后进行10天的BZYQ治疗。通过流式细胞术、qPCR、蛋白质免疫印迹法和体外骨髓来源巨噬细胞（BMDM）培养验证抗炎作用。
在BZYQ中鉴定出54种化合物，其中7种SPCs（黄芪甲苷、甘草黄酮A、18β-甘草次酸、光甘草定、灵芝酸X、车叶草苷和异樱花素）与UC发病机制直接相关。分子对接证实光甘草定与白细胞介素-6（IL-6）之间存在高亲和力相互作用。BZYQ通过抑制IL-6/信号转导与转录激活因子3（STAT3）轴、重新编程巨噬细胞极化、增加调节性T细胞频率和抑制初始CD4 T细胞分化来减轻结肠炎。
本研究首次明确了BZYQ在缓解UC中的成分基础和细胞免疫机制。这些发现有助于中药方剂的开发与应用。
